Tumor necrosis factor-α promoter variant 2 (TNF2) is associated with pre-term delivery, infant mortality, and malaria morbidity in western Kenya: Asembo Bay Cohort Project IX
Article first published online: 12 OCT 2001
Copyright © 2001 Wiley-Liss, Inc.
Volume 21, Issue 3, pages 201–211, November 2001
How to Cite
Aidoo, M., McElroy, P. D., Kolczak, M. S., Terlouw, D. J., ter Kuile, F. O., Nahlen, B., Lal, A. A. and Udhayakumar, V. (2001), Tumor necrosis factor-α promoter variant 2 (TNF2) is associated with pre-term delivery, infant mortality, and malaria morbidity in western Kenya: Asembo Bay Cohort Project IX. Genet. Epidemiol., 21: 201–211. doi: 10.1002/gepi.1029
- Issue published online: 12 OCT 2001
- Article first published online: 12 OCT 2001
- Manuscript Accepted: 7 MAR 2001
- Manuscript Received: 18 JAN 2001
- NCID/Emerging Infectious Disease Funds (V.U.)
- premature birth
A polymorphism in the promoter region of the tumor necrosis factor-α (TNF-α) gene, with a guanine to adenine nucleotide change at position –308, TNF2 is associated with increased TNF-α production. TNF2 homozygotes have a higher risk of severe disease and/or death due to cerebral malaria and other infectious diseases. We investigated the impact of this allele on malaria morbidity and mortality in young children who participated in an immuno-epidemiologic cohort study of malaria in an area of intense perennial Plasmodium falciparum transmission in western Kenya. A total of 1,048 children were genotyped. Poisson regression and Cox proportional hazards models were used to determine the relationship between TNF-308 variants and morbidity and mortality. The gene frequencies of the TNF1 and TNF2 alleles were 0.90 and 0.10, respectively. TNF2 homozygosity was associated with pre-term birth when compared with TNF1 homozygotes [relative risk (RR) 7.3, 95% CI, 2.85–18.9, P = 0.002) and heterozygotes (RR 6.7, 95% CI 2.0–23.0, P = 0.008). Among children born prematurely, the TNF2 allele was significantly associated with a higher risk of death in infancy compared with TNF1 (RR 7.47, 95% CI 2.36–23.6). The risk of death was higher among TNF2 homozygotes than among heterozygotes. The TNF2 allele was significantly associated with high density P. falciparum parasitemia (RR 1.11, 95% CI 1.0–1.24). Among low birth weight children, the TNF2 allele was associated with severe anemia (RR 2.16, 95% CI 1.17–4.01) and showed a trend toward a risk for severe malaria anemia (RR 1.99, 95% CI 0.89–4.46). These data suggest that TNF2 is a risk factor for pre-term birth and early childhood mortality and malaria morbidity in children in this region. Further understanding of the pathogenic mechanisms underlying this association is required. Genet. Epidemiol. 21:201–211, 2001. © 2001 Wiley-Liss, Inc.